Patent GB-593734-A (GB)
Title: Manufacture of substituted alkylene dicarboxylic acid diamides
IPC: C07D295/185
Filed: 1943-12-17
Abstract: Substituted alkylene dicarboxylic acid diamides are produced by reacting in the presence or absence of solvents, condensation agents and acid binding agents alkylene dicarboxylic acids which in the alkylene group contain at least one mono- or bivalent carbon - bound aliphatic cyclo - aliphatic or heterocyclic residue (the alkylene group, if linked with a monovalent cycloaliphatic residue, containing only one carbon atom; any bivalent residue being only linked with one carbon atom of the alkylene group and containing at least two carbon atoms, and any saturated or unsaturated aliphatic residue containing less than five carbon atoms), or functional derivatives, e.g. esters, halides or anhydrides of such dicarboxylic acids with secondary aliphatic or cycloaliphatic amines which contain at least three carbon atoms or with secondary heterocyclic amines or by reacting salts of the dicarboxylic acids with carbamic acid halides which are derived from secondary aliphatic or cycloaliphatic amines of at least three carbon atoms or from secondary heterocyclic amines.  The rings of the cyclo-aliphatic or heterocyclic residues may be linked with the alkylene group directly or by an aliphatic binding link and two aliphatic residues located on the same carbon atom of the alkylene group may be closed in ring form by carbon or hetero atom linkage. Additional methods are to treat the metal compounds of substituted-alkylene dicarboxylic acid diamides derived from ammonia or primary amines, the metal compounds being obtained by means of, e.g. sodium amide, with alkylating or cyclo-alkylating agents or in the case of malonic acid derivatives to start with malonic acid tetra-substituted diamides which in the methylene group contain replaceable hydrogen, converting these diamides into their metal compounds, e.g. by means of sodium, sodium ethylate or sodium amide and treating these compounds with a reactive ester of a hydroxyl compound, e.g. the hydrohalic acid or sulphuric acid esters capable of introducing the desired constituent.  Suitable starting materials are, for example, dimethyl malonic acid, methyl-ethyl-, diethyl-, allyl-methyl-, propyl-methyl-, isopropyl - methyl-, methyl - isopropenyl- and isopropylidene malonic acids, a  : a -dimethyl-, a : a -diethyl-, a  : a -methyl-ethyl-, tetramethyl-and a  - methyl - b - ethyl-, succinic acids, b  : b -dimethyl-, a  : a  - dimethyl - a : a  : a 1 - trimethyl-and a  : a  : b -trimethyl-glutaric acids, tetramethyl adipic acid, cyclohexyl-, cyclo-hexyl-methyl- and cyclohexenyl-malonic acids, cyclopentylidene malonic acid (obtainable by condensation of malonic acid with cyclopentanone), furfurylidene - malonic acid, cyclo - propane-, -butane-, -pentane-, -hexane-1 : 1-dicarboxylic acid, tetrahydropyrandicarboxylic acid - (4 : 4), N - ethyl- and N - cyclohexyl - 2 : 6 - dimethyl - piperidine-dicarboxylic acid - (4 : 4) (obtainable by converting the dilactone of bis-(b -hydroxy propyl)-malonic acid with phosphorus pentachloride into bis-(b -chloro-propyl)-malonic acid dichloride, the latter being converted by heating with water to the free acid, and reacting this with ethylamine or cyclohexylamine respectively, the products being treated with acetic acid to yield the free acid), b -morpholinoethyl-methyl-malonic acid (obtainable by condensation of b -morpholinoethylchloride with methyl malonic acid ester and subsequent saponification).  As condensation agents, phosphorus halides, phosphorus pentoxide, thionyl chloride or phosgene are preferably used.  In examples, methyl-isopropenyl malonic acid is treated with phosphorus pentachloride and the acid chloride then treated with diethylamine in dry ether and the diethylamino - hydrochloride drawn off.  The residue is freed of any residual amount of the latter by means of lye and potash; (2) malonic acid bis-diethyl amide is heated with sodium amide and then with n-propyl bromide.  The n-propyl-malonic acid heated with sodium amide and then with n-bis-diethyl amide is precipitated with potash. Alkyl-n-propyl-malonic acid bisdiethyl amides may be produced in this way or from alkyl-n-propyl-malonic acid diamides by ethylation; (3) the acid chloride of tetrahydropyran dicarboxylic acid (4 : 4) is treated with diethylamine.  The analogous sulphur compound can be used instead of the tetrahydropyran compound, being obtained from dichlorodiethyl sulphide and malonic ester; (4) assymetric dimethyl succinic acid chloride is reacted with diethyl amine to obtain a  : a -dimethyl succinic acid bis-diethyl amide.  This is also obtained by reacting diethyl-carbamic acid chloride with the sodium salt of a  : a -dimethyl succinic acid; (5) b  : b -dimethyl glutaric acid bis-diethyl amide is obtained from b  : b -dimethyl-glutaric acid chloride and diethyl amine.  Several additional products produced from aliphatic, cycloaliphatic and secondary heterocyclic amines and the acids specified above are described.  The Specification as open to inspection under Sect. 91 states that the substituents in the alkylene group may be any carbon-bound organic residue including aromatic and hydroaromatic residues and malonic acid substituted by one tetrahydropyran radical is specified as a suitable acid.  This subject-matter does not appear in the Specification as accepted.